This proposal is designed to address one of the most immediate problems in leprosy research; understanding the immune response to M. leprae. Such studies might lead to effective vaccination, protecting millions of people at risk from Hansen's disease. A second objective is to evaluate two immunotherapy regimens which might improve the condition of patients already diseased. Vaccination would be the optimal way to approach the problem of world-wide-leprosy; however, the immune response to this disease is so variable and imperfectly understood that wide-spread vaccination programs designed without greater basic understanding of the immune response to M. leprae in immunocompetent individuals might not be successful. We plan to approach this problem in two ways: 1) We will continue to study the immune response by which the immunocompetent mouse infected with M. leprae limits multiplication of the infecting bacilli, and we will attempt to elucidate the specific mechanisms by which the animal accomplishes permanent control of his disease. We will assess delayed type hypersensitivity in vivo and examine various in vitro correlates of cell mediated immunity such as the ability of lymphocytes to respond to specific antigens by blastogenesis, to act as cytotoxic cells against various targets and to produce lymphokines. 2) To assess whether immunocompetent cells or human dialyzable transfer factor (TFd) enable the infected mouse to kill the organisms more quickly or to eliminate them once they are dead, we will treat infected mice by two immunotherapy regimens designed to ascertain whether immunocompetent lymphocytes from the popliteal lymph node draining and infection can act cytotoxically against M. leprae or against M. leprae-infected macrophages in vivo, and whether TFd can effect a change in the immune response of the M. leprae-infected mouse.